The present invention relates to formulation of a bio-absorbable proteinaceous matrix derived from animal tissue. The invention also relates to the use of this matrix in vivo which functions to induce and facilitate the growth and generation/regeneration of tissue.
With the exception of blood, all other tissues in the body are composed of cells arranged in an integrated structure which requires an extracellular support scaffold or matrix in order to maintain proper growth differentiation and function. The field of tissue engineering aims to provide methods of achieving the complex structure using either artificial or natural polymers with properties that allow cell attachment, growth and pattern formation in order to provide replacement tissues for those lost during injury or disease. The ideal scaffolding material would be non-immunogenic and mimic the natural scaffold support structure found in the body as closely as possible. One of these attributes is that the scaffold be biodegradable to allow for regenerated or restored tissue to reach its ultimate level of homeostasis and function. It is known in the prior art to construct bioabsorbable scaffolds capable of providing support structure for cellular attachments and growth as well as delivery of biologically active chemicals, proteins, and peptides. The most widely used are hydrogels composed of various polymers including polysaccharides. Biodegradable hydrogels produced from biodegradable polysaccharides either alone or in combination with naturally occurring extracellular matrix proteins such as collagen have been employed as vehicles for drug delivery (Cascone, M. G. et al., Bioartificial polymeric materials based on polysaccharides, J Biomater. Sci. Polym. Ed. 12, 267-281, 2001; Jeong, B. et al., Drug release from biodegradable injectable thermosensitive hydrogel of PEG-PLGA-PEG triblock copolymers, J Control Release 63, 155-163, 2000; Kopecek, J., Smart and genetically engineered biomaterials and drug delivery systems, Eur. J. Pharm. Sci. 20, 1-16, 2003; Peppas, N. A. et al., Hydrogels in pharmaceutical formulations, Eur. J. Pharm. Biopharm. 50, 27-46, 2000; Zhang, Y., and Chu, C. C., In vitro release behavior of insulin from biodegradable hybrid hydrogel networks of polysaccharide and synthetic biodegradable polyester, J. Biomater. Appl. 16, 305-325, 2002) and providing structural support for engineered tissues (Arevalo-Silva, C. A. et al., Internal support of tissue-engineered cartilage, Arch. Otolaryngol. Head Neck Surg. 126, 1448-1452, 2000; Desgrandchamps, F., Biomaterials in functional reconstruction, Curr. Opin. Urol. 10, 201-206, 2000; Kim, T. K. et al., Experimental model for cartilage tissue engineering to regenerate the zonal organization of articular cartilage, Osteoarthritis Cartilage 11, 653-664, 2003; Kojima, K. et al., A composite tissue-engineered trachea using sheep nasal chondrocyte and epithelial cells, Faseb J. 17, 823-828, 2003; Marler, J. J. et al., Soft-tissue augmentation with injectable alginate and syngeneic fibroblasts, Plast. Reconstr. Surg. 105, 2049-2058, 2000; Saim, A. B. et al., Engineering autogenous cartilage in the shape of a helix using an injectable hydrogel scaffold, Laryngoscope 110, 1694-1697, 2000; Thompson, C. A. et al., Percutaneous transvenous cellular cardiomyoplasty: A novel nonsurgical approach for myocardial cell transplantation, J. Am. Coll. Cardiol. 41, 1964-1971, 2003; Wake, M. C. et al., Dynamics of fibrovascular tissue ingrowth in hydrogel foams, Cell Transplant. 4, 275-279, 1995; Weng, Y. et al., Tissue-engineered composites of bone and cartilage for mandible condylar reconstruction, J. Oral Maxillofac. Surg. 59, 185-190, 2001; Zimmermann, U. et al., Hydrogel-based non-autologous cell and tissue therapy, Biotechniques 29, 564-572, 574, 576 passim, 2000). Recently, the use of hydrogel scaffold as a bridging structure capable of providing guidance channels for regenerating neural tissue for treatment of spinal cord injury (“SCI”) has been reported (Tsai, E. C. et a., Synthetic hydrogel guidance channels facilitate regeneration of adult rat brainstem motor axons after complete spinal cord transection, J. Neurotrauma. 21, 789-804, 2004;). The production of an extracellular matrix or scaffolding material from blood or other tissue has been described by Vacanti and Vacanti (Biological Scaffolding Material, US Patent Publication Number 20040137613, filed Oct. 17, 2003). This material is described as being composed substantially of cells, cellular debris and cells remnants. However, this material is not reported to possess a biological functionality that facilitates wound repair or regeneration and furthermore requires viable cells or other structures with cell-like properties (Vacanti, M. P. et al., Identification and initial characterization of spore-like cells in adult mammals, J. Cell Biochem. 80, 455-460, 2001). Notwithstanding these achievements, there remains a need for a non-immunogenic (or reduced-immunogenic) scaffolding material that further possesses cellular attachment, growth promoting properties, and supports or stimulates regenerative/restorative properties of uninjured tissues surrounding would sites.